title: Serum interleukin-6 levels in metastatic renal cell carcinoma before treatment with interleukin-2 correlates with paraneoplastic syndromes but not patient survival.
abstract: OBJECTIVE
  We sought to determine the frequency of interleukin-6 (IL-6) expression in renal cancer cell lines, the frequency of the detection of IL-6 in the serum of patients with metastatic renal cell carcinoma, whether serum IL-6 level correlates with the development of paraneoplastic syndromes and whether serum IL-6 level in patients with metastatic renal cancer correlates with response to treatment with interleukin-2 (IL-2) or patient survival.
  
  
  METHODS
  Conditioned media from 21 cell lines from 20 patients were examined for IL-6. We identified 2 matched groups of patients with metastatic renal cancer (30 responders and 29 nonresponders) to IL-2 based immunotherapy. Stored pretreatment serum specimens were evaluated for IL-6. Medical records were reviewed to determine the presence of paraneoplastic syndromes.
  
  
  RESULTS
  IL-6 was detected in 19 of 21 renal cancer cell lines (90%) obtained from 20 patients with metastatic renal cancer as well as in the serum of 33 of 59 patients (56%) with metastatic renal cell carcinoma. A significant association between serum IL-6 level and anemia (p = 0.0032), elevated platelet count (p = 0.01), decreased albumin (p = 0.034) and elevated alkaline phosphatase (p = 0.04) was found. A trend was noted of the association of increased serum IL-6 level and fever (p = 0.051). No correlation was found between pretreatment serum IL-6 level and survival or response to IL-2.
  
  
  CONCLUSIONS
  IL-6 was frequently secreted by renal cancer cell lines but it was only present in the serum of approximately half of the patients with metastatic renal cancer. Elevations of serum IL-6 were associated with paraneoplastic manifestations frequently seen in patients with renal cancer, including anemia, thrombocytosis, decreased albumin and elevations of alkaline phosphatase (Stauffer's syndrome). A weak relationship was noted between serum IL-6 level and fever but none was noted between that and survival or response to IL-2.
authors.affiliation: Surgery Branch, National Cancer Institute, Bethesda, Maryland, USA.
authors.forename: M M
authors.initials: MM
authors.lastname: Walther
authors.forename: B
authors.initials: B
authors.lastname: Johnson
authors.forename: D
authors.initials: D
authors.lastname: Culley
authors.forename: R
authors.initials: R
authors.lastname: Shah
authors.forename: J
authors.initials: J
authors.lastname: Weber
authors.forename: D
authors.initials: D
authors.lastname: Venzon
authors.forename: J C
authors.initials: JC
authors.lastname: Yang
authors.forename: W M
authors.initials: WM
authors.lastname: Linehan
authors.forename: S A
authors.initials: SA
authors.lastname: Rosenberg
mesh_terms: D000328:Adult; D000368:Aged; D002292:Carcinoma, Renal Cell / Q000097:blood* / Q000401:mortality / Q000556:secondary* / Q000628:therapy; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007376:Interleukin-2 / Q000627:therapeutic use*; D015850:Interleukin-6 / Q000097:blood* / Q000378:metabolism; D007680:Kidney Neoplasms / Q000097:blood* / Q000401:mortality / Q000473:pathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D010257:Paraneoplastic Syndromes / Q000097:blood*; D016019:Survival Analysis; D016896:Treatment Outcome; D014407:Tumor Cells, Cultured
chemical_list: D017077:Culture Media, Conditioned; D007155:Immunologic Factors; D007376:Interleukin-2; D015850:Interleukin-6